The enzyme glutaminase in the membranes of mitochondria, i.e., organelles producing energy of cells, is known as one of the enzymes that are characteristically required for the proliferation of some tumor cells and utilized only in a trace amount in other normal cells. Researchers have not succeeded in developing clinically satisfactory anti-cancer agents that, by inhibiting this enzyme, selectively inhibit the proliferation of tumor cells and cause no damage to other cells (e.g., Medina et al., "Miguel Angel Medina": Molecular and Cellular Biochemistry, 113, 1-15 (1992)).
The number of patients with a large intestinal cancer (e.g., colon carcinoma, rectum carcinoma) is the largest next to that of patients with lung carcinoma, and the large intestinal cancer has a high postoperative recurrence rate. At present, there is no postoperative auxiliary chemotherapeutic agent that is effective alone. Combinations of conventional chemotherapeutic agents, e.g., mainly the antimetabolite 5-fluorouracil (5-FU), have been used for the therapy. However, effective standard therapies against the disease have not been established yet (see e.g., "Carcinoma of the Colon and Rectum", Medical View, 1989). Novel selective therapeutic agents against large intestinal cancers are being developed all over the world. However, clinically effective ones have not developed yet (e.g., Colon Cancer Cells, p.1, M. P. Moyer and G. H. Poste ed., Academic Press, Inc., (1990)).
The following compounds are known.
(1) The compound (A) described in Cancer Research, 53, 3172-3178, Jul. 1, 1993: ##STR1## (2) The compound (B) described in JP-A 62-7732, JP-A 3-17064, Biochemical Pharmacology, Vol. 43, No. 8, pp. 1717-1723, 1992: ##STR2## (3) The compound (C) described in JP-A 3-5461: ##STR3## Ar=phenyl, alkyl, etc. (4) The compound (D) described in FR-2681323-A1: ##STR4## R.sup.1, R.sup.2 =optionally protected amino (5) The compound (E) described in Biochemical Society Transactions, 14, 1053-1054, 1986: ##STR5##
The above compounds (A), (B), (C) and (D) have different chemical structures and action mechanisms from those of the compound in the present invention. There is no description that the compound (E) inhibits glutaminase and selectively inhibits the proliferation of tumor cells.
Thus, there is a need for highly selective therapeutic agents that have potent inhibitory activity against the proliferation of tumor cells and have no toxicity to normal in vivo tissues.